rs8072451

Positions:

• chr17-45816350-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004382.5(CRHR1):​c.122-113C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,407,280 control chromosomes in the GnomAD database, including 29,871 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (2223 hom., cov: 33)
  • Exomes 𝑓: 0.20 (27648 hom.)
• Consequence: CRHR1 NM_004382.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90

Genes affected

CRHR1 (HGNC:2357): (corticotropin releasing hormone receptor 1) This gene encodes a G-protein coupled receptor that binds neuropeptides of the corticotropin releasing hormone family that are major regulators of the hypothalamic-pituitary-adrenal pathway. The encoded protein is essential for the activation of signal transduction pathways that regulate diverse physiological processes including stress, reproduction, immune response and obesity. Alternative splicing results in multiple transcript variants. Naturally-occurring readthrough transcription between this gene and upstream GeneID:147081 results in transcripts that encode isoforms that share similarity with the products of this gene. [provided by RefSeq, Aug 2016]

LINC02210-CRHR1 (HGNC:51483): (LINC02210-CRHR1 readthrough) This locus represents naturally occurring readthrough transcription between neighboring genes CRHR1-IT1, CRHR1 intronic transcript 1 (Gene ID: 147081) and CRHR1, corticotropin releasing hormone receptor 1 (Gene ID: 1394) on chromosome 17. The readthrough transcript encodes a protein that shares sequence identity with the product of the CRHR1 gene. [provided by RefSeq, Dec 2016]

CRHR1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRHR1	NM_004382.5	c.122-113C>T		intron_variant		ENST00000314537.10	NP_004373.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRHR1	ENST00000314537.10	c.122-113C>T		intron_variant		1	NM_004382.5	ENSP00000326060.6
LINC02210-CRHR1	ENST00000634540.1	c.-404-113C>T		intron_variant		2		ENSP00000488912.1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23165 AN: 152078 Hom.: 2225 Cov.: 33

Gnomad AFR AF: 0.0741

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0737

Gnomad FIN AF: 0.0649

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.190

GnomAD4 exome AF: 0.199 AC: 249867 AN: 1255084 Hom.: 27648 AF XY: 0.196 AC XY: 121627 AN XY: 621308

Gnomad4 AFR exome AF: 0.0691

Gnomad4 AMR exome AF: 0.131

Gnomad4 ASJ exome AF: 0.252

Gnomad4 EAS exome AF: 0.000853

Gnomad4 SAS exome AF: 0.0806

Gnomad4 FIN exome AF: 0.0753

Gnomad4 NFE exome AF: 0.226

Gnomad4 OTH exome AF: 0.182

GnomAD4 genome AF: 0.152 AC: 23164 AN: 152196 Hom.: 2223 Cov.: 33 AF XY: 0.142 AC XY: 10596 AN XY: 74412

Gnomad4 AFR AF: 0.0741

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0738

Gnomad4 FIN AF: 0.0649

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.187

Alfa AF: 0.188 Hom.: 800

Bravo AF: 0.159

Asia WGS AF: 0.0330 AC: 117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.014
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs8072451; hg19: chr17-43893716;